Deciphering of <i>Candida parapsilosis</i> induced immune response in <i>Drosophila melanogaster</i>

<i>Candida</i> infections are the most prevalent cause of serious human mycoses and are the third most common pathogens isolated from bloodstream infections in hospitalized patients. <i>C. parapsilosis</i> is a member of the <i>non-albicans</i> spp., which have a predilection for causing life-threatening disease in neonates and hospitalized pediatric patients. In this study, we utilized a <i>Drosophila melanogaster</i> infection model to analyze the immunological responses to <i>C. parapsilosis</i>. Our results demonstrate that the Toll pathway in <i>Drosophila</i> controls <i>C. parapsilosis</i> proliferation as the Toll signaling mutant <i>MyD88^−/</i>⁻ flies are highly susceptible to <i>C. parapsilosis</i>. We also confirmed that the <i>MyD88^−/</i>⁻ fly is a convenient invertebrate animal model to analyze virulence properties of different species and strains from the <i>C. parapsilosis sensu lato</i> complex as <i>C. orthopsilosis, C. metapsilosis</i> proved to be less virulent than <i>C. parapsilosis sensu stricto</i> and the <i>N</i>-mannan deficient <i>C. parapsilosis och1</i>Δ/Δ strain showed attenuated pathogenicity in this immunodeficient <i>Drosophila</i> background. We also found that Persephone protease is not required for detection and activation of Toll pathway during <i>C. parapsilosis</i> infection. Furthermore, we observed that <i>Drosophila</i> β-glucan receptor deficient flies where more sensitive to <i>C. parapsilosis</i> compared to wild-type flies; however, we could not find a clear dependence on the recognition of this receptor and the cell wall β-glucan exposure-induced host response. These studies establish this <i>D. melanogaster</i> infection model as an efficient tool in deciphering immune responses to <i>C. parapsilosis</i> as well as for assessing virulence factors produced by this emerging fungal predator.